James E . Ferrell

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Ca(2+) signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-trisphosphate and the release of Ca(2+) from intracellular stores. An elusive signaling process senses the Ca(2+) store depletion and triggers the opening of plasma membrane Ca(2+) channels. The resulting sustained Ca(2+) signals are required for(More)
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to(More)
It is becoming increasingly clear that bistability (or, more generally, multistability) is an important recurring theme in cell signaling. Bistability may be of particular relevance to biological systems that switch between discrete states, generate oscillatory responses, or "remember" transitory stimuli. Standard mathematical methods allow the detection of(More)
Recent experimental work has shown that the mitogen-activated protein (MAP) kinase cascade can convert graded inputs into switch-like outputs. The cascade could therefore filter out noise (signals of insufficient magnitude or duration) and still respond decisively to supra-threshold stimuli. Here, we explore the biochemical mechanisms likely to be at the(More)
In the early embryonic cell cycle, Cdc2–cyclin B functions like an autonomous oscillator, whose robust biochemical rhythm continues even when DNA replication or mitosis is blocked. At the core of the oscillator is a negative feedback loop; cyclins accumulate and produce active mitotic Cdc2–cyclin B; Cdc2 activates the anaphase-promoting complex (APC); the(More)
A simple negative feedback loop of interacting genes or proteins has the potential to generate sustained oscillations. However, many biological oscillators also have a positive feedback loop, raising the question of what advantages the extra loop imparts. Through computational studies, we show that it is generally difficult to adjust a negative feedback(More)
Cell signaling systems that contain positive-feedback loops or double-negative feedback loops can, in principle, convert graded inputs into switch-like, irreversible responses. Systems of this sort are termed "bistable". Recently, several groups have engineered artificial bistable systems into Escherichia coli and Saccharomyces cerevisiae, and have shown(More)
Neurite extension and branching are important neuronal plasticity mechanisms that can lead to the addition of synaptic contacts in developing neurons and changes in the number of synapses in mature neurons. Here we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates movement, extension, and branching of filopodia and fine dendrites as(More)
A typical protein kinase must recognize between one and a few hundred bona fide phosphorylation sites in a background of ∼700,000 potentially phosphorylatable residues. Multiple mechanisms have evolved that contribute to this exquisite specificity, including the structure of the catalytic site, local and distal interactions between the kinase and substrate,(More)
Xenopus oocytes convert a continuously variable stimulus, the concentration of the maturation-inducing hormone progesterone, into an all-or-none biological response-oocyte maturation. Here evidence is presented that the all-or-none character of the response is generated by the mitogen-activated protein kinase (MAPK) cascade. Analysis of individual oocytes(More)